Assessment of the cortisol awakening response: Real-time analysis and curvilinear effects of sample timing inaccuracy

The cortisol awakening response (CAR) is typically measured in the domestic setting. Moderate sample timing inaccuracy has been shown to result in erroneous CAR estimates and such inaccuracy has been shown partially to explain inconsistency in the CAR literature. The need for more reliable measurement of the CAR has recently been highlighted in expert consensus guidelines where it was pointed out that less than 6% of published studies provided electronic-monitoring of saliva sampling time in the post-awakening period. Analyses of a merged data-set of published studies from our laboratory are presented. To qualify for selection, both time of awakening and collection of the first sample must have been verified by electronic-monitoring and sampling commenced within 15 min of awakening. Participants (n = 128) were young (median age of 20 years) and healthy. Cortisol values were determined in the 45 min post-awakening period on 215 sampling days. On 127 days, delay between verified awakening and collection of the first sample was less than 3 min (‘no delay’ group); on 45 days there was a delay of 4–6 min (‘short delay’ group); on 43 days the delay was 7–15 min (‘moderate delay’ group). Cortisol values for verified sampling times accurately mapped on to the typical post-awakening cortisol growth curve, regardless of whether sampling deviated from desired protocol timings. This provides support for incorporating rather than excluding delayed data (up to 15 min) in CAR analyses. For this population the fitted cortisol growth curve equation predicted a mean cortisol awakening level of 6 nmols/l (±1 for 95% CI) and a mean CAR rise of 6 nmols/l (±2 for 95% CI). We also modelled the relationship between real delay and CAR magnitude, when the CAR is calculated erroneously by incorrectly assuming adherence to protocol time. Findings supported a curvilinear hypothesis in relation to effects of sample delay on the CAR. Short delays of 4–6 min between awakening and commencement of saliva sampling resulted an overestimated CAR. Moderate delays of 7–15 min were associated with an underestimated CAR. Findings emphasize the need to employ electronic-monitoring of sampling accuracy when measuring the CAR in the domestic setting.

External quality assessment of BRAF molecular analysis in melanoma

The availability of BRAF inhibitors has given metastatic melanoma patients an effective new treatment choice and molecular testing to determine the presence or absence of a BRAF codon 600 mutation is pivotal in the clinical management of these patients. This molecular test must be performed accurately and appropriately to ensure that the patient receives the most suitable treatment in a timely manner. Laboratories have introduced such testing; however, some experience low sample throughput making it critical that an external quality assurance programme is available to help promote a high standard of testing, reporting and provide an educational aspect for BRAF molecular testing. Laboratories took part in three rounds of external quality assessment (EQA) during a 12-month period giving participants a measure of the accuracy of genotyping, clinical interpretation of the result and experience in testing a range of different samples. Formalin fixed paraffin embedded tissue sections from malignant melanoma patients were distributed to participants for BRAF molecular testing. The standard of testing was generally high but distribution of a mutation other than the most common, p.(Val600Glu), highlighted concerns with detection or reporting of the presence of rarer mutations. The main issues raised in the interpretation of the results were the importance of clear unambiguous interpretation of the result tailored to the patient and the understanding that the treatment is different from that given to other stratified medicine programmes. The variability in reporting and wide range of methodologies used indicate a continuing need for EQA in this field.

Communication and behavior in high reliability organizations: An Analysis of Communication in Civil Aviation

Communication can be seen as one of the most important features to manage conflicts and the stress of the work teams that operate in environments with strong pressure, complex operations and continuous risk, which are aspects that characterize a high reliability organization. This article aims to highlight the importance of communication in high-reliability organizations, having as object of study the accidents and incidents in civil aviation area. It refers to a qualitative research, outlined by documental analysis based on investigations conducted by the Federal Aviation Administration and the Center of Investigation and Prevention of Aeronautical Accidents. The results point out that human errors account for 60 to 80 percent of accidents and incidents. Most of these occurrences are attributed to miscommunication between the professionals involved with the air and ground operation, such as pilots, crewmembers and maintenance staff, and flight controllers. Inappropriate tone of voice usage, difficulties to understand different accents between the issuer and the receiver or even difficulty to perceive red flags between the lines of verbal and non-verbal communication, are elements that contribute to the fata of understanding between people involved in the operation. As a research limitation this present research pointed out a lack of a special category of "interpersonal communications failures" in the official agency reports. So, the researchers must take the conceptual definition of "social ability", communication implied, to classify behaviors and communication matters accordingly. Other research finding indicates that communication is superficially approached in the contents of air operations courses what could mitigate the lack of communications skills as a social ability. Part of the research findings refers to the contents of communication skills development into the program to train professional involved in air flight and ground operations. So, it is expected that this present article gives an appropriate highlight towards the improvement of flight operations training programs. Developing communication skills among work teams in high reliability organizations can contribute to mitigate stress, accidents and incidents in Civil Aviation Field. The original contribution of this article is the proposal of the main contents that should be developed in a Communication Skills Training Program, specially addressed to Civil Aviation operations.

Madeira wine vinification process: analysis and control

The present study was done in collaboration with J. Faria e Filhos company, a Madeira wine producer, and its main goal was to fully characterize three wines produced during 2014 harvest and identify possible improving points in the winemaking process. The winemaking process was followed during 4 weeks, being registered the amounts of grapes received, the fermentation temperatures, the time at which fermentation was stopped and evolution of must densities until the fortification time. The characterization of musts and wines was done in terms of density, total and volatile acidity, alcohol content, pH, total of polyphenol, organic acids composition, sugars concentration and the volatile profile. Also, it was developed and validated an analytical methodology to quantify the volatile fatty acids, namely using SPME-GC-MS. Briefly, the following key features were obtained for the latter methodology: linearity (R2=0.999) e high sensitivity (LOD =0.026-0.068 mg/L), suitable precision (repeatability and reproducibility lower than 8,5%) and good recoveries (103,11-119,46%). The results reveal that fermentation temperatures should be controlled in a more strictly manner, in order to ensure a better balance in proportion of some volatile compounds, namely the esters and higher alcohols and to minimize the concentration of some volatiles, namely hexanoic, octanoic and decanoic acids, that when above their odours threshold are not positive for the wine aroma. Also, regarding the moment to stop the fermentation, it was verified that it can be introduced changes which can also be benefit to guarantee the tipicity of Madeira wine bouquet.

Ultrasonic Spectral Analysis for Nuclear Fuel Characterization

Ceramic materials have been widely used for various purposes in many different industries due to certain characteristics, such as high melting point and high resistance to corrosion. Concerning the areas of applications, automobile, aeronautics, naval and even nuclear, the characteristics of these materials should be strictly controlled. In the nuclear area, ceramics are of great importance once they are the nuclear fuel pellets and must have, among other features, a well controlled porosity due to mechanical strength and thermal conductivity required by the application. Generally, the techniques used to characterize nuclear fuel are destructive and require costly equipment and facilities. This paper aims to present a nondestructive technique for ceramic characterization using ultrasound. This technique differs from other ultrasonic techniques because it uses ultrasonic pulse in frequency domain instead of time domain, associating the characteristics of the analyzed material with its frequency spectrum. In the present work, 40 Alumina (Al2O3) ceramic pellets with porosities ranging from 5% to 37%, in absolute terms measured by Archimedes technique, were tested. It can be observed that the frequency spectrum of each pellet varies according to its respective porosity and microstructure, allowing a fast and non-destructive association of the same characteristics with the same spectra pellets.

Shakedown Analysis Considering Limited Kinematic Hardening Materials

In design or safety assessment of mechanical structures, the use of the Design by Analysis (DBA) route is a modern trend. However, for making possible to apply DBA to structures under variable loads, two basic failure modes considered by ASME or European Standards must be precluded. Those modes are the alternate plasticity and incremental collapse (with instantaneous plastic collapse as a particular case). Shakedown theory is a tool that permit us to assure that those kinds of failures will be avoided. However, in practical applications, very large nonlinear optimization problems are generated. Due to this facts, only in recent years have been possible to obtain algorithms sufficiently accurate, robust and efficient, for dealing with this class of problems. In this paper, one of these shakedown algorithms, developed for dealing with elastic ideally-plastic structures, is enhanced to include limited kinematic hardening, a more realistic material behavior. This is done in the continuous model by using internal thermodynamic variables. A corresponding discrete model is obtained using an axisymmetric mixed finite element with an internal variable. A thick wall sphere, under variable thermal and pressure loads, is used in an example to show the importance of considering the limited kinematic hardening in the shakedown calculations

Adapting prospective structural analysis to strengthen sustainable management and capacity building in community-based natural resource management contexts

Local communities collectively managing common pool resources can play an important role in sustainable management, but they often lack the skills and context-specific tools required for such management. The complex dynamics of social-ecological systems (SES), the need for management capacities, and communities’ limited empowerment and participation skills present challenges for community-based natural resource management (CBNRM) strategies. We analyzed the applicability of prospective structural analysis (PSA), a strategic foresight tool, to support decision making and to foster sustainable management and capacity building in CBNRM contexts and the modifications necessary to use the tool in such contexts. By testing PSA in three SES in Colombia, Mexico, and Argentina, we gathered information regarding the potential of this tool and its adaptation requirements. The results suggest that the tool can be adapted to these contexts and contribute to fostering sustainable management and capacity building. It helped identify the systems’ dynamics, thus increasing the communities’ knowledge about their SES and informing the decision-making process. Additionally, it drove a learning process that both fostered empowerment and built participation skills. The process demanded both time and effort, and required external monitoring and facilitation, but community members could be trained to master it. Thus, we suggest that the PSA technique has the potential to strengthen CBNRM and that other initiatives could use it, but they must be aware of these requirements.

Exploring the Impact of a Difficult Breastfeeding Experience on Maternal Identity: A Narrative Analysis

Introduction: Due to the implied health benefits for mother and baby, breastfeeding has become a key public health issue. Literature reviewed highlighted the ‘medical’ and ‘natural’ mother discourse which surrounds motherhood and impacts on women’s decisions to breastfeed. Whilst the emotional and physical strains of a difficult experience have been explored, it is unclear how these experiences impact on women’s identities as mothers and in what ways women are able to narrate and share their embodied experiences. Methods: Seven first time mothers who described themselves as having had a difficult breastfeeding experience were interviewed to gather data pertaining to how mothers construct narratives of breastfeeding and the impact of these narratives on their identity as mothers. An interest in both socio-political discourse and embodiment theory derived from the literature review led to the use of visual methods in eliciting narratives and the employment of a critical narrative analysis in exploring the data gathered. Findings: The participants’ narratives drew from ‘medical’ and ‘natural’ mother discourses and were found to constrain subjective experience and leave participants with feelings of guilt, frustration and loss. A prevailing assumption that unruly, excessive bodies must be controlled by a rational ‘mind’ led to the body becoming a site for control and resistance for participants as they attempted to conform to norms of motherhood and breastfeeding. Discussion: Results identified the ways in which women as mothers can see their subjective experiences diminished and their voices silenced due to a lack of available discourse and entrenched ideologies surrounding the ‘good’ mother. It is suggested that adopting a social justice agenda within therapeutic practice might prevent the internalisation of oppressive discourse which can lead to mothers’ psychological distress. Moreover, it is suggested that exploring the body in therapy might resist a mind/body dualism and lead to increasingly compassionate and accepting relationships with our bodies; in turn increasing awareness of subjective experience.

An overview on how failure analysis contributes to flight safety in the Portuguese Air Force

Failure analysis has been, throughout the years, a fundamental tool used in the aerospace sector, supporting assessments performed by sustainment and design engineers mainly related to failure modes and material suitability. The predicted service life of aircrafts often exceeds 40 years, and the design assured life rarely accounts for all in service loads and in service environmental menaces that aging aircrafts must deal with throughout their service lives. From the most conservative safe-life conceptual design approaches to the most recent on-condition based design approaches, assessing the condition and predicting the failure modes of components and materials are essential for the development of adequate preventive and corrective maintenance actions as well as for the accomplishment and optimization of scheduled maintenance programs of aircrafts. Moreover, as the operational conditions of aircrafts may vary significantly from operator to operator (especially in military aircraft), it is necessary to access if the defined maintenance programs are adequate to guarantee the continuous reliability and safe usage of the aircrafts, preventing catastrophic failures which bear significant maintenance and repair costs, and that may lead to the loss of human lives. Thus being, failure analysis and material investigations performed as part of aircraft accidents and incidents investigations arise as powerful tools of the utmost importance for safety assurance and cost reduction within the aeronautical and aerospace sectors. The Portuguese Air Force (PRTAF) has operated different aircrafts throughout its long existence, and in some cases, has operated a particular type of aircraft for more than 30 years, gathering a great amount of expertise in: assessing failure modes of the aircrafts materials; conducting aircrafts accidents and incidents investigations (sometimes with the participation of the aircraft manufacturers and/or other operators); and in the development of design and repair solutions for in-service related problems. This paper addresses several studies to support the thesis that failure analysis plays a key role in flight safety improvement within the PRTAF. It presents a short summary of developed

Phylum-wide transcriptome analysis of oogenesis and early embryogenesis in selected nematode species

Oogenesis is a prerequisite for embryogenesis in Metazoa. During both biological processes important decisions must be made to form the embryo and hence ensure the next generation: (1) Maternal gene products (mRNAs, proteins and nutrients) must be supplied to the embryo. (2) Polarity must be established and axes must be specified. While incorporation of maternal gene products occurs during oogenesis, the time point of polarity establishment and axis specification varies among species, as it is accomplished either prior, during, or after fertilisation. But not only the time point when these events take place varies among species but also the underlying mechanisms by which they are triggered. For the nematode model Caenorhabditis elegans the underlying pathways and gene regulatory networks (GRNs) are well understood. It is known that there the sperm entry point initiates a primary polarity in the 1-celled egg and with it the establishment of the anteroposterior axis. However, studies of other nematodes demonstrated that polarity establishment can be independent of sperm entry (Goldstein et al., 1998; Lahl et al., 2006) and that cleavage patterns, symmetry formation and cell specification also differ from C. elegans. In contrast to the studied Chromadorea (more derived nematodes including C. elegans), embryos of some marine Enoplea (more basal representatives) even show no discernible early polarity and blastomeres can adopt variable cell fates (Voronov and Panchin 1998). The underlying pathways controlling the obviously variant embryonic processes in non-Caenorhabditis nematodes are essentially unknown. In this thesis I addressed this issue by performing a detailed unbiased comparative transcriptome analysis based on microarrays and RNA sequencing of selected developmental stages in a variety of nematodes from different phylogenetic branches with C. elegans as a reference system and a nematomorph as an outgroup representative. In addition, I made use of available genomic data to determine the presence or absence of genes for which no expression had been detected. In particular, I focussed on components of selected pathways or GRNs which are known to play essential roles during C. elegans development and/or other invertebrate or vertebrate model systems. Oogenesis must be regulated differently in non-Caenorhabditis nematodes, as crucial controlling components of Wnt and sex determination signaling are absent in these species. In this respect, I identified female-specific expression of potential polarity associated genes during gonad development and oogenesis in the Enoplean nematode Romanomermis culicivorax. I could show that known downstream components of the polarity complexes PAR-3/-6/PKC-3 and PAR-1/-2 are absent in non-Caenorhabditis species. Even PAR-2 as part of the polarity complex does not exist in these nematodes. Instead, transcriptomes of nematodes (including C. elegans), show expression of other polarity-associated complexes such as the Lgl (Lethal giant larvae) complex. This result could pose an alternative route for nematodes and nematomorphs to initiate polarity during early embryogenesis. I could show that crucial pathways of axis specification, such as Wnt and BMP are very different in C. elegans compared to other nematodes. In the former, Wnt signaling, for instance, is mediated by four paralogous beta-catenins, while other Chromadorea have fewer and Enoplea only one beta-catenin. The transcriptomes of R. culicivorax and the nematomorph show that regulators of BMP (e.g. Chordin), are specifically expressed during early embryogenesis only in Enoplea and the close outgroup of nematomorphs. In conclusion, my results demonstrate that the molecular machinery controlling oogenesis and embryogenesis in nematodes is unexpectedly variable and C. elegans cannot be taken as a general model for nematode development. Under this perspective, Enoplean nematodes show more similarities with outgroups than with C. elegans. It appears that certain pathway components were lost or gained during evolution and others adopted new functions. Based on my findings I can conjecture, which pathway components may be ancestral and which were newly acquired in the course of nematode evolution.

Threat analysis of IoT networks using artificial neural network intrusion detection system

The Internet of things (IoT) is still in its infancy and has attracted much interest in many industrial sectors including medical fields, logistics tracking, smart cities and automobiles. However, as a paradigm, it is susceptible to a range of significant intrusion threats. This paper presents a threat analysis of the IoT and uses an Artificial Neural Network (ANN) to combat these threats. A multi-level perceptron, a type of supervised ANN, is trained using internet packet traces, then is assessed on its ability to thwart Distributed Denial of Service (DDoS/DoS) attacks. This paper focuses on the classification of normal and threat patterns on an IoT Network. The ANN procedure is validated against a simulated IoT network. The experimental results demonstrate 99.4% accuracy and can successfully detect various DDoS/DoS attacks.

Incorporation of Hysteretic Effects in Model-Order Reduction Analysis of Magnetic Devices

The ability to predict the properties of magnetic materials in a device is essential to ensuring the correct operation and optimization of the design as well as the device behavior over a wide range of input frequencies. Typically, development and simulation of wide-bandwidth models requires detailed, physics-based simulations that utilize significant computational resources. Balancing the trade-offs between model computational overhead and accuracy can be cumbersome, especially when the nonlinear effects of saturation and hysteresis are included in the model. This study focuses on the development of a system for analyzing magnetic devices in cases where model accuracy and computational intensity must be carefully and easily balanced by the engineer. A method for adjusting model complexity and corresponding level of detail while incorporating the nonlinear effects of hysteresis is presented that builds upon recent work in loss analysis and magnetic equivalent circuit (MEC) modeling. The approach utilizes MEC models in conjunction with linearization and model-order reduction techniques to process magnetic devices based on geometry and core type. The validity of steady-state permeability approximations is also discussed.

Analysis of Molecular Dynamics Simulations of Protein Folding

Microsecond long Molecular Dynamics (MD) trajectories of biomolecular processes are now possible due to advances in computer technology. Soon, trajectories long enough to probe dynamics over many milliseconds will become available. Since these timescales match the physiological timescales over which many small proteins fold, all atom MD simulations of protein folding are now becoming popular. To distill features of such large folding trajectories, we must develop methods that can both compress trajectory data to enable visualization, and that can yield themselves to further analysis, such as the finding of collective coordinates and reduction of the dynamics. Conventionally, clustering has been the most popular MD trajectory analysis technique, followed by principal component analysis (PCA). Simple clustering used in MD trajectory analysis suffers from various serious drawbacks, namely, (i) it is not data driven, (ii) it is unstable to noise and change in cutoff parameters, and (iii) since it does not take into account interrelationships amongst data points, the separation of data into clusters can often be artificial. Usually, partitions generated by clustering techniques are validated visually, but such validation is not possible for MD trajectories of protein folding, as the underlying structural transitions are not well understood. Rigorous cluster validation techniques may be adapted, but it is more crucial to reduce the dimensions in which MD trajectories reside, while still preserving their salient features. PCA has often been used for dimension reduction and while it is computationally inexpensive, being a linear method, it does not achieve good data compression. In this thesis, I propose a different method, a nonmetric multidimensional scaling (nMDS) technique, which achieves superior data compression by virtue of being nonlinear, and also provides a clear insight into the structural processes underlying MD trajectories. I illustrate the capabilities of nMDS by analyzing three complete villin headpiece folding and six norleucine mutant (NLE) folding trajectories simulated by Freddolino and Schulten [1]. Using these trajectories, I make comparisons between nMDS, PCA and clustering to demonstrate the superiority of nMDS. The three villin headpiece trajectories showed great structural heterogeneity. Apart from a few trivial features like early formation of secondary structure, no commonalities between trajectories were found. There were no units of residues or atoms found moving in concert across the trajectories. A flipping transition, corresponding to the flipping of helix 1 relative to the plane formed by helices 2 and 3 was observed towards the end of the folding process in all trajectories, when nearly all native contacts had been formed. However, the transition occurred through a different series of steps in all trajectories, indicating that it may not be a common transition in villin folding. The trajectories showed competition between local structure formation/hydrophobic collapse and global structure formation in all trajectories. Our analysis on the NLE trajectories confirms the notion that a tight hydrophobic core inhibits correct 3-D rearrangement. Only one of the six NLE trajectories folded, and it showed no flipping transition. All the other trajectories get trapped in hydrophobically collapsed states. The NLE residues were found to be buried deeply into the core, compared to the corresponding lysines in the villin headpiece, thereby making the core tighter and harder to undo for 3-D rearrangement. Our results suggest that the NLE may not be a fast folder as experiments suggest. The tightness of the hydrophobic core may be a very important factor in the folding of larger proteins. It is likely that chaperones like GroEL act to undo the tight hydrophobic core of proteins, after most secondary structure elements have been formed, so that global rearrangement is easier. I conclude by presenting facts about chaperone-protein complexes and propose further directions for the study of protein folding.

Non-comital women of twelfth-century England: a charter based analysis

This thesis sets out to explore the place and agency of non-comital women in twelfth-century Anglo-Norman England. Until now, broad generalisations have been applied to all aristocratic women based on a long established scholarship on royal and comital women. Non-comital women have been overlooked, mainly because of an assumed lack of suitable sources from this time period. The first aim of this thesis is to demonstrate that there is a sufficient corpus of charters for a study of this social group of women. It is based on a database created from 5545 charters, of which 3046 were issued by non-comital women and men, taken from three case study counties, Oxfordshire, Suffolk and Yorkshire, and is also supported by other government records. This thesis demonstrates that non-comital women had significant social and economic agency in their own person. By means of a detailed analysis of charters and their clauses this thesis argues that scholarship on non-comital women must rethink the framework applied to the study of non-comital women to address the lifecycle as one of continuities and as active agents in a wider public society. Non-comital women’s agency and identity was not only based on land or in widowhood, which has been the one period in their life cycles where scholars have recognised some level of autonomy, and women had agency in all stages of their life cycle. Women’s agency and identity were drawn from and part of a wider framework that included their families, their kin, and broader local political, religious, and social networks. Natal families continued to be important sources of agency and identity to women long after they had married. Part A of the thesis applies modern charter diplomatic analysis methods to the corpus of charters to bring out and explore women’s presence therein. Part B contextualises these findings and explores women’s agency in their families, landholding, the gift-economy, and the wider religious and social networks of which they were a part.

Spectral Frame Analysis and Learning through Graph Structure

This dissertation investigates the connection between spectral analysis and frame theory. When considering the spectral properties of a frame, we present a few novel results relating to the spectral decomposition. We first show that scalable frames have the property that the inner product of the scaling coefficients and the eigenvectors must equal the inverse eigenvalues. From this, we prove a similar result when an approximate scaling is obtained. We then focus on the optimization problems inherent to the scalable frames by first showing that there is an equivalence between scaling a frame and optimization problems with a non-restrictive objective function. Various objective functions are considered, and an analysis of the solution type is presented. For linear objectives, we can encourage sparse scalings, and with barrier objective functions, we force dense solutions. We further consider frames in high dimensions, and derive various solution techniques. From here, we restrict ourselves to various frame classes, to add more specificity to the results. Using frames generated from distributions allows for the placement of probabilistic bounds on scalability. For discrete distributions (Bernoulli and Rademacher), we bound the probability of encountering an ONB, and for continuous symmetric distributions (Uniform and Gaussian), we show that symmetry is retained in the transformed domain. We also prove several hyperplane-separation results. With the theory developed, we discuss graph applications of the scalability framework. We make a connection with graph conditioning, and show the in-feasibility of the problem in the general case. After a modification, we show that any complete graph can be conditioned. We then present a modification of standard PCA (robust PCA) developed by Cand\`es, and give some background into Electron Energy-Loss Spectroscopy (EELS). We design a novel scheme for the processing of EELS through robust PCA and least-squares regression, and test this scheme on biological samples. Finally, we take the idea of robust PCA and apply the technique of kernel PCA to perform robust manifold learning. We derive the problem and present an algorithm for its solution. There is also discussion of the differences with RPCA that make theoretical guarantees difficult.